Compounds of the formula: wherein R and R′ are the same or different hydroxy protecting group; are intermediates to pharmaceutically active compounds (see, e.g., U.S. Pat. Nos. 4,075,227, 4,133,814, 4,418,068, 5,552,401 and 5,723,474).
According to the procedures described in the above mentioned patents and other literature references, these intermediates are constructed via an acid catalyzed cyclodehydration reaction of a compound of the formula: 
Said cyclodehydration reaction results in an initial mixture of 6- and 4-OR isomers (nomenclature refers to the position of the OR group on the benzothiophene ring) which lie in equilibrium with a pair of corresponding aryl migrated isomers. These isomers and their relationship to each other are illustrated below where the #(#) nomenclature refers first to the position of the OR group on the benzothiophene ring and refers second to the position of the phenyl-OR′ group on the benzothiophene ring: 
The art teaches that the above cyclodehydration can be catalyzed with certain acids including mineral and organic acids such as polyphosphoric, phosphoric and methanesulfonic acid, acidic cation exchange resins such as Amberlyst 15, and Lewis acids such as boron trifluoride etherate (see, e.g., Tet. Let., 40:2909, 1999; Org. Proc. Res. & Dev., 3:56, 1999; and U.S. Pat. No.'s 4,358,593, 5,512,684, 5,969,157 and 5,977,383). The use of said acids result in varying 6 to 4-OR isomer ratios and also vary in their amenability toward isolating the 3-aryl isomers, particularly the 6(3) isomer.
For example, when polyphosphoric, phosphoric or methanesulfonic acid is employed, and R and R′ are both methyl, the 6 to 4-OR isomer ratio ranges from about 75:25 to about 80:20. Furthermore, when these acids are employed, it is difficult to isolate either of the initial cyclization products since the 2-aryl/3-aryl isomer equilibrium is quickly established and favors the 2-aryl isomer.
When Amberlyst 15 is employed, the rearrangement reaction is approximately fifty to a hundred times slower than the cyclization and hence the 3-aryl isomer can be isolated if desired. However, upon consumption of the cyclization starting material (about 7 hours when R and R′ are both methyl and with a 10% weight loading of the Amberlyst 15 resin), a significant amount of the 3-aryl isomer (about 7.4%) has rearranged to the 2-aryl isomer. Similarly, when one of R or R′ is hydrogen and the other is methyl about 8.1% of the 3-aryl isomer in both cases has rearranged to the 2-aryl isomer. Moreover, use of Amberlyst 15 affords about a 88:12 in situ mixture of 6 and 4-OR isomers when R and R′ are methyl, a ratio of 88:12 when R is hydrogen and R′ is methyl and 90:10 when R is methyl and R′ is hydrogen.
Although the 3-aryl isomer is accessible when boron trifluoride is employed, in order to obtain reasonable yields the reaction must be run neat. Furthermore, use of this acid on a compound where R and R′ are both methyl results in 6 to 4-OR isomer ratios comparable to that of polyphosphoric acid (about 6:1). Work-up and product isolation requires quenching and removing the acid via solvent extractions.